Pharmacology of the new reversible inhibitor of monoamine oxidase A, RS-8359.
RS-8359 is a new reversible inhibitor of monoamine oxidase A (RIMA). With a selectivity ratio of about 2200 for the A:B enzyme types, it is one of the most specific of this class of compounds. As a result, it shows relatively little effect upon blood pressure when administered together with tyramine, thus effectively eliminating the 'cheese' effect which has contributed to the limited clinical use of the classical monoamine oxidase inhibitors (MAOIs). RS-8359 shows little affinity for the common central nervous system receptors and little anticholinergic effect. These characteristics suggest a relatively benign adverse event profile, which may be particularly advantageous in the elderly and may generally contribute to patient acceptance and compliance. In terms of its effects upon serotonin (5-hydroxytryptamine), RS-8359 gives increases similar to those of other MAOIs with activity sustained for about 9 h. In behavioural investigations, the compound gives results similar to those found with several antidepressants widely used in the clinic. Overall, the pharmacology of RS-8359 indicates that it should have antidepressant activity in man.
Iwata
N
N
Sankyo Co., Ltd, Tokyo, Japan.
Püchler
K
K
Plenker
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017982:Receptors, Biogenic Amine / Q000187:drug effects / Q000378:metabolism; D012110:Reserpine / Q000037:antagonists & inhibitors; D015656:Respiratory Mechanics / Q000187:drug effects; D013237:Stereoisomerism
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D002492:Central Nervous System Depressants; D008996:Monoamine Oxidase Inhibitors; D009570:Nitriles; D011743:Pyrimidines; D017982:Receptors, Biogenic Amine; C059590:RS 8359; D012110:Reserpine